In-vivo selection of the mutation F121Y in a patient failing raltegravir containing salvage regimen

Autor(es)

Cavalcanti, Jaqueline Souza ^[1] ; Lanca, Andre Minhoto ; de Paula Ferreira, Joao Leandro ; da Eira, Margareth ^[2] ; de Souza Dantas, Daniel Soares ^[2] ; de Macedo Brigido, Luis Fernando

Afiliação do(s) autor(es)

^[1] Adolfo Lutz Inst, Ctr Virol, Lab Retrovirus, BR-01246902 Sao Paulo, SP - Brazil

^[2] Inst Infectol Emilio Ribas, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Antiviral Research; v. 95, n. 1, p. 9-11, JUL 2012.
• Citações Web of Science: 6

Resumo

Raltegravir is an integrase inhibitor (INI) licensed for clinical use and other INI are in advanced stage of development. Different resistance mutations in HIV integrase from patients using these antiretroviral drugs have been described and G148H/R/K, N155H and less frequently Y143C/H/R are considered major resistant mutations to raltegravir. Both Stanford Database and Geno2Pheno list F121Y as conferring intermediate resistance ``in vitro{''} both to raltegravir and elvitegravir. We report for the first time the ``in vivo{''} selection F121Y and evolution to Y143R in a 31 years old male clade B HIV-1 infected patient failing a raltegravir-containing salvage regimen. Plasma samples nine months prior to raltegravir (RAL-Naive) and at weeks 32, 40 and 88 after RAL-containing regimen were analyzed. Antiretroviral susceptibility was evaluated at Stanford and Geno2Pheno from sequences obtained with RT-PCR. After a Viral load at week 12 below 50 copies/mL, viremia raised at week 20 to 4.510g10. The emergence of F121Y was observed at week 32 and 40, alongside with L74I, T97A, Q137H and V151I. At week 88 F121Y was no longer detected, L74I and T97A were maintained and Y143R emerged. F121Y might be an alternative pathway to Y143R. Changing of RAL-containing regimen upon the identification of F121Y might avoid the evolution of raltegravir resistance. (C) 2012 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 11/21958-2 - Resistência genotípica no resgate terapêutico de pacientes infectados pelo HIV-1 com novas classes de antirretrovirais
• Beneficiário: Luís Fernando de Macedo Brígido
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/61311-0 - Avaliação do teste de genotipagem do HIV e terapias de resgate no estado de São Paulo
• Beneficiário: Rosangela Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisa em Políticas Públicas para o SUS